Autoimmune responses to antigens of spermatozoa occur after vasectomy in men and in experimental animals. It has been hypothesized that such responses are caused by leakage of spermatozoal antigens from the vas deferens, other regions of the excurrent tract and perhaps even the seminiferous tubules. However, no data are available on the actual site(s) of antigen leakage. Therefore, we propose to investigate this problem in vasectomized rabbits and determine how sensitizaton to spermatozoa initially occurs. The information obtained will be useful in clarifying the sequence of events taking place after vasectomy in rabbits and men. The data may also apply to immune responses against spermatozoa often observed in infertile, nonvasectomized men, since recent studies of testicular biopsies obtained from both infertile and vasectomized men have shown a similarity of histopathological and immunopathological findings between men and rabbits. In the three years of requestied support we plan to: 1. Study the occurrecne of permeability changes in the testis and the excurrent tract following vasectomy. These experiments will be performed by perfusion with fluorescent tracers (dextrans of different molecular weight, labeled with fluorescein isothyocyanate). 2. Identify the site(s) of leakage of spermatozoal antigens after vasectomy. These investigations will be performed by perfusion with radiolabeled antibodies to antigens of spermatozoa, followed by autoradiography to identify sites of antigen-antibody binding. 3. Correlate both permeability changes and leakage of antigens with autoimmune responses to spermatozoa (both humoral and cell-mediated) and autoimmune orchitis.